ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 14L

Safety and Efficacy of ABT-494, a Novel Selective JAK1 Inhibitor, in Patients with Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Anti-TNF Biologic Therapy

Joel M. Kremer1, Edward C. Keystone2, Paul Emery3, Heidi S. Camp4, Alan Friedman4, Li Wang4, Ahmed A. Othman4, Nasser Khan4 and Steven Jungerwirth4, 1Albany Medical College, Albany, NY, 2Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, 3NIHR-Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, United Kingdom, 4AbbVie Inc., North Chicago, IL

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: October 27, 2015

Keywords: , , , ,

Session Information

Date: Tuesday, November 10, 2015

Title: ACR Late-breaking Abstract Poster Presentations

Session Type: ACR Late-breaking Abstract Session

Session Time: 9:00AM-11:00AM

Background/Purpose: The safety, efficacy,
and dose response of ABT-494, a novel selective JAK1 inhibitor, were characterized
vs placebo (PBO) in patients (pts) with moderately to severely active RA and an
inadequate response to ≥1
anti-TNF biologic therapy (TNF-IR).   Methods:
This
was a phase 2b, 12-week, double‐blind PBO-controlled study; TNF-IR pts receiving
stable background methotrexate (MTX) were randomized 1:1:1:1:1 to ABT‐494 3, 6, 12,
and 18 mg twice daily (BID) or matching PBO. The primary efficacy endpoint was
the proportion of pts who achieved an ACR20 response at week 12.   Results:
All
276 pts had failed ≥1 anti-TNF therapy prior to enrollment; 28% had received
≥2 anti-TNF biologics and 20% had also received non–anti-TNF biologics. Baseline
(BL) characteristics were similar in all treatment groups. The proportion of pts
achieving ACR20 at week 12 was significantly higher for all ABT-494 groups vs PBO
(Table 1). There was a significant (P<0.01) dose response
between PBO and all ABT-494 treatment groups for ACR20 response rates (non-responder
imputation) at week 12. ACR50 and ACR70 responses were statistically
significantly higher at doses of ≥6 mg BID. Changes in DAS28(CRP) from BL
were significantly greater for all doses of ABT-494 vs PBO. Onset of action was
rapid, with significant differences in ACR20 and change in DAS28(CRP) from BL at
week 2 (P≤0.007) for 6, 12, and 18 mg BID vs PBO. Low disease
activity and clinical remission per DAS28(CRP) criteria were achieved
statistically significantly more often in the 12-mg BID dose group vs PBO. The
incidences of AEs were numerically higher in ABT-494 dose groups, with some trend
towards dose dependency (Table 2). The majority of infections were mild.
There was one serious infection (“bronchiectasis”) in the PBO group and none in
the ABT-494 treatment groups were reported. Five pts had non-serious events of
herpes zoster: 1 pt each in the ABT-494 3 mg, 12 mg, and 18 mg BID treatment
groups, and 2 pts in the PBO group. One pt in the 6-mg BID dose group reported
2 events of non-melanoma skin cancer (basal cell and squamous cell carcinomas).
There was 1 report of anemia in the 18-mg BID dose group. No deaths were
reported during the study. Conclusion: This phase 2b
study demonstrated the clinical efficacy of ABT-494 vs PBO when dosed in combination
with MTX in TNF-IR pts with active RA. ABT-494 had an acceptable safety and
tolerability profile.    

Table 1. Efficacy Endpoints at Week 12
  PBO (n=56) ABT-494
3 mg BID (n=55) 6 mg BID (n=55) 12 mg BID (n=55) 18 mg BID (n=55)

ACR20, %

34

53*

58**

71***

67***

ACR50, %

16 24 35* 42** 38**

ACR70, %

4 13 26** 22** 22**
DAS28(CRP), mean change from baseline† -1.1 -1.9** -2.2*** -2.5*** -2.3***

CR DAS28 <2.6, %

13

24

26

33*

27

LDA DAS28 <3.2, %

25

33

36

49**

42

LDA CDAI ≤10, %

25

27

31

40

40

ACR20/50/70, 20%/50%/70% improvement in American College of Rheumatology score; BID, twice daily; CDAI, Clinical Disease Activity Index; CR, clinical remission; CRP, C-reactive protein; DAS28, 28-joint Disease Activity Score; LDA, low disease activity. Non-responder imputation (NRI) unless otherwise noted. ***, **, *: statistically significant at the 0.001, 0.01, and 0.05 levels.

†Last observation carried forward.

   

Table 2. Adverse Events Summary
Number of pts, n (%) PBO (n=56) ABT-494
3 mg BID (n=55) 6 mg BID (n=55) 12 mg BID (n=55) 18 mg BID (n=55)
Any AE 25 (45) 26 (47) 31 (56) 37 (67) 39 (71)
Serious AE 1 (2) 2 (4) 2 (4) 0 1 (2)
Severe AE 2 (4) 1 (2) 2 (4) 2 (4) 1 (2)
AE leading to discontinuation 2 (4) 0 6 (11) 2 (4) 3 (6)
Infections

13 (23)

11 (20)

12 (22)

22 (40)

21 (38)

Serious infection

1 (2)

0

0

0

0

Anemia 0 0 0 0 1 (2)
Herpes zoster 2 (4) 1 (2) 0 1 (2) 1 (2)
Hepatic disorder 1 (2) 0 0 0 2 (4)
Neutropenia 0 0 0 1 (2) 1 (2)
Malignancy 0 0 1 (2) 0 0
AE, adverse event; BID, twice daily.

 

Disclosure: J. M. Kremer, Corrona, 1,AbbVie, Lilly, Novartis, and Pfizer, 2,Corrona, 3,Corrona, 4,AbbVie, Lilly, Pfizer, Medimmune, Sanofi, and Regeron, 5; E. C. Keystone, AbbVie and Lilly, 2,AbbVie and Lilly, 5,AbbVie and Lilly, 8; P. Emery, Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, and Lilly, 2,Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, and Lilly, 5; H. S. Camp, AbbVie Inc., 3,AbbVie Inc., 1; A. Friedman, AbbVie Inc., 3,AbbVie Inc., 1; L. Wang, AbbVie Inc., 3,AbbVie Inc., 1; A. A. Othman, AbbVie Inc., 3,AbbVie Inc., 1; N. Khan, AbbVie Inc., 3,AbbVie Inc., 1; S. Jungerwirth, AbbVie Inc., 3,AbbVie Inc., 1.

To cite this abstract in AMA style:

Kremer JM, Keystone EC, Emery P, Camp HS, Friedman A, Wang L, Othman AA, Khan N, Jungerwirth S. Safety and Efficacy of ABT-494, a Novel Selective JAK1 Inhibitor, in Patients with Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Anti-TNF Biologic Therapy [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/safety-and-efficacy-of-abt-494-a-novel-selective-jak1-inhibitor-in-patients-with-active-rheumatoid-arthritis-and-inadequate-response-or-intolerance-to-anti-tnf-biologic-therapy/. Accessed .

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